Design and synthesis of a SAM-based inhibitor for protein arginine methyl transferase (PRMT) enzymes

David Weldon, Bryan Knuckley, Corey P. Causey

Department of Chemistry and Biochemistry, University of North Florida

The protein arginine methyl transferases (PRMTs) catalyzed the addition of methyl groups from S-adenosylmethionine (SAM) to the guanidinium group of arginine residues. This post-translational modification, which often occurs on histone proteins, has putative roles in the onset and progression of some cancers, making these enzymes a potential target for therapeutic intervention. We have recently reported peptide-based inhibitors that demonstrate isozyme specificity derived from sequence information. Herein we report the design of a novel PRMT inhibitor that uses the structure of SAM as the scaffold.